Questa pagina è stata tradotta automaticamente e l'accuratezza della traduzione non è garantita. Si prega di fare riferimento al Versione inglese per un testo di partenza.

La valutazione di PC14586 in pazienti con tumori solidi avanzati che ospitano una mutazione p53 Y220C

1 ottobre 2026 aggiornato da: PMV Pharmaceuticals, Inc

Uno studio multicentrico in aperto di fase 1/2 per valutare la sicurezza, la tollerabilità, la farmacocinetica, la farmacodinamica e l'efficacia di PC14586 in pazienti con tumori solidi avanzati che ospitano una mutazione p53 Y220C (PYNNACLE)

The Phase 2 monotherapy portion of this study is currently enrolling and will evaluate the efficacy and safety of PC14586 (INN rezatapopt) in participants with locally advanced or metastatic solid tumors harboring a TP53 Y220C mutation. The Phase 1 portion of the study will assess the safety, tolerability and preliminary efficacy of multiple dose levels of rezatapopt as monotherapy and in Phase 1b in combination with pembrolizumab.

Panoramica dello studio

Stato

Reclutamento

Condizioni

Intervento / Trattamento

Descrizione dettagliata

Rezatapopt is a first-in-class, oral, small molecule p53 reactivator that is selective for the TP53 Y220C mutation.

The primary objective of Phase 2 Monotherapy is to evaluate the efficacy of rezatapopt at the Recommended Phase 2 Dose (RP2D) including the Overall Response Rate (ORR) in the Ovarian Cancer Cohort and the ORR across all cohorts as determined by blinded independent central review. Secondary objectives of Phase 2 are to characterize the safety, pharmacokinetic (PK) properties, quality of life, and other efficacy measures of PC14586 rezatapopt at the RP2D. Enrollment is open for the Phase 2 Monotherapy portion of the study.

The primary objective of Phase 1 Monotherapy is to establish the maximum tolerated dose (MTD) and RP2D of rezatapopt. Secondary objectives are to characterize the PK properties, safety and tolerability, and to assess preliminary efficacy including ORR. Enrollment into Phase 1 Monotherapy is complete.

The primary objective of Phase 1b Combination Therapy is to establish the MTD/RP2D of rezatapopt when administered in combination with pembrolizumab. Secondary objectives of Phase 1b Combination Therapy are to characterize PK, safety and tolerability, and to assess preliminary efficacy of rezatapopt when administered in combination with pembrolizumab, including ORR. Enrollment into Phase 1b Combination Therapy is complete.

Tipo di studio

Interventistico

Iscrizione (Stimato)

300

Fase

  • Fase 2
  • Fase 1

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Contatto studio

Luoghi di studio

  • Australia
    • New South Wales
      • Camperdown, New South Wales, Australia
        • Reclutamento
        • Chris O'Brien Lifehouse Hospital
        • Contatto:
          • Peter Grimison, MD
    • Queensland
      • South Brisbane, Queensland, Australia
        • Reclutamento
        • Mater Cancer Care Centre
        • Contatto:
          • Catherine Shannon, MD
    • South Australia
      • Bedford Park, South Australia, Australia
        • Reclutamento
        • Flinders Medical Center
        • Contatto:
          • Shawgi Sukumaran, MD
    • Victoria
      • Clayton, Victoria, Australia
        • Reclutamento
        • Monash Medical Centre
        • Contatto:
          • Sophia Frentzas, MD
    • Western Australia
      • Nedlands, Western Australia, Australia
        • Reclutamento
        • Linear Clinical Research
        • Contatto:
          • Michael Millward, MD
  • Corea del Sud
      • Seoul, Corea del Sud
        • Reclutamento
        • Samsung Medical Center
        • Contatto:
          • Chel Hun Choi, MD
      • Seoul, Corea del Sud
        • Reclutamento
        • Asan Medical Center
        • Contatto:
          • Dae Ho Lee, MD
      • Seoul, Corea del Sud
        • Reclutamento
        • Seoul University Hospital
        • Contatto:
          • Seock-Ah Im, MD
      • Seoul, Corea del Sud
        • Reclutamento
        • Severance Hospital Yonsei University
        • Contatto:
          • Jung-Yun Lee, MD
      • Seoul, Corea del Sud
        • Reclutamento
        • National Cancer Center
        • Contatto:
          • Myong Cheol Lim, MD, PhD
  • Francia
      • Lyon, Francia
        • Reclutamento
        • Centre Léon Bérard Centre Régional de Lutte Contre Le Cancer
        • Contatto:
          • Isabelle Ray-Coquard, MD
      • Nîmes, Francia, 30900
        • Reclutamento
        • CHU de Nîmes
        • Contatto:
          • Frédéric Fiteni, MD, PhD
      • Vandœuvre-lès-Nancy, Francia, 54519
        • Reclutamento
        • Institute Cancer De Lorraine
        • Contatto:
          • Aurélien Lambert, MD
    • Bas-Rhin
      • Strasbourg, Bas-Rhin, Francia
        • Reclutamento
        • ICANS - Institut de cancérologie Strasbourg Europe
        • Contatto:
          • Lauriane Eberst, MD
    • Gironde
      • Bordeaux, Gironde, Francia
        • Reclutamento
        • Institut Bergonie
        • Contatto:
          • Veronique Debien, MD
    • Haute-Garonne
      • Toulouse, Haute-Garonne, Francia
        • Reclutamento
        • Institut Claudius Regaud
        • Contatto:
          • Carlos-Alberto Gomez-Roca, MD
    • Loire-Atlantique
      • Saint-Herblain, Loire-Atlantique, Francia
        • Reclutamento
        • EDOG Institut de Cancerologie de l'Ouest
        • Contatto:
          • Jean-Sebastien Frenel, MD
    • Puy-de-Dôme
      • Clermont-Ferrand, Puy-de-Dôme, Francia
        • Reclutamento
        • Centre Jean Perrin
        • Contatto:
          • Xavier Durando, MD
    • Val-de-Marne
      • Villejuif, Val-de-Marne, Francia
        • Reclutamento
        • Institut Gustave Roussy
        • Contatto:
          • Yohann Loriot, MD
  • Germania
    • Baden-Wurttemberg
      • Heidelberg, Baden-Wurttemberg, Germania
        • Reclutamento
        • Nationale Centrum für Tumorerkrankungen (NCT) Heidelberg
        • Contatto:
          • Martin Haag, MD
    • Bavaria
      • Augsburg, Bavaria, Germania
        • Reclutamento
        • Universitätsklinikum Augsburg
        • Contatto:
          • Rainer Claus, MD
    • Free and Hanseatic City of Hamburg
      • Hamburg, Free and Hanseatic City of Hamburg, Germania
        • Reclutamento
        • Asklepios Klinik Altona
        • Contatto:
          • Dirk Arnold, MD
    • Hesse
      • Frankfurt am Main, Hesse, Germania
        • Ritirato
        • Universitätsklinikum Frankfurt
    • North Rhine-Westphalia
      • Essen, North Rhine-Westphalia, Germania
        • Reclutamento
        • Universitätsklinikum Essen
        • Contatto:
          • Marcel Wiesweg, MD
  • Italia
      • Milan, Italia
        • Reclutamento
        • Humanitas San Pio X
        • Contatto:
          • Domenica Lorusso, MD
      • Naples, Italia, 80131
        • Reclutamento
        • IRCCS - lstituto Nazionale Tumori - Fondazione G. Pascale
        • Contatto:
          • Anna Passarelli, MD
    • Lazio
      • Rome, Lazio, Italia
        • Reclutamento
        • Fondazione Policlinico Universitario Agostino Gemelli IRCCS
        • Contatto:
          • Anna Fagotti, MD
      • Rome, Lazio, Italia
        • Reclutamento
        • Istituti Fisioterapici Ospitalieri - Istituto Nazionale Tumori Regina Elena
        • Contatto:
          • Lorenza Landi, MD
    • Lombardy
      • Milan, Lombardy, Italia
        • Reclutamento
        • ASST Grande Ospedale Metropolitano Niguarda
        • Contatto:
          • Salvatore Siena, MD
      • Milan, Lombardy, Italia
        • Reclutamento
        • Fondazione IRCCS Istituto Nazionale Dei Tumori
        • Contatto:
          • Massimo Di Nicola, MD
      • Milan, Lombardy, Italia
        • Reclutamento
        • Istituto Europeo Di Oncologia
        • Contatto:
          • Giuseppe Curigliano, MD
      • Rozzano, Lombardy, Italia
        • Reclutamento
        • Istituto Clinico Humanitas
        • Contatto:
          • Armando Santoro, MD
    • Torino
      • Candiolo, Torino, Italia
        • Reclutamento
        • Fondazione del Piemonte per l'Oncologia (IRCCS)
        • Contatto:
          • Chiara Lazzari, MD
  • Regno Unito
    • Middlesex
      • London, Middlesex, Regno Unito
        • Reclutamento
        • Sarah Cannon Research Institute UK
        • Contatto:
          • Elisa Fontana, MD, PhD
    • Tyne and Wear
      • Newcastle upon Tyne, Tyne and Wear, Regno Unito
        • Reclutamento
        • Freeman Hospital
        • Contatto:
          • Alastair Greystoke, MB ChB PhD
  • Singapore
      • Kent Ridge, Singapore
        • Reclutamento
        • National University Hospital
        • Contatto:
          • David Shao Peng Tan, MD
      • Singapore, Singapore, 168582
        • Reclutamento
        • National Cancer Center of Singapore
        • Contatto:
          • Tira Tan, MD
  • Spagna
      • Barcelona, Spagna
        • Reclutamento
        • NEXT Oncology-Hospital Quironsalud Barcelona
        • Contatto:
          • Elena Garralda, MD
      • Barcelona, Spagna
        • Reclutamento
        • Instituto de Investigacion Oncologica Vall d'Hebron (VHIO) - EPON
        • Contatto:
          • Lorena Farinas, MD
      • Madrid, Spagna, 28041
        • Reclutamento
        • Hospital Universitario 12 de Octubre
        • Contatto:
          • Santiago Ponce Aix, MD
      • Rioja, Spagna
        • Reclutamento
        • START Rioja
        • Contatto:
          • Jorge Luis Ramon Patino, MD
      • Valencia, Spagna
        • Reclutamento
        • Hospital Clinico Universitario de Valencia
        • Contatto:
          • José Alejandro Pérez Fidalgo, MD
    • Madrid
      • Madrid, Madrid, Spagna
        • Reclutamento
        • START MADRID_Hospital Universitario Fundacion Jimenez Diaz
        • Contatto:
          • Victor Moreno Garcia, MD
      • Madrid, Madrid, Spagna
        • Reclutamento
        • START MADRID_Hospital Universitario HM Sanchinarro - CIOCC
        • Contatto:
          • Irene Moreno, MD
  • Stati Uniti
    • California
      • Irvine, California, Stati Uniti, 92868
        • Ritirato
        • University of California Irvine Chao Family Comprehensive Cancer Center
      • La Jolla, California, Stati Uniti, 92093
        • Reclutamento
        • University of San Diego Moores Cancer Center
        • Contatto:
          • Shumei Kato, MD
      • Los Angeles, California, Stati Uniti, 90033
        • Reclutamento
        • USC Norris Comprehensive Cancer Center
        • Contatto:
          • Anthony El-Khoueiry, MD
      • Los Angeles, California, Stati Uniti, 90024
        • Reclutamento
        • UCLA Jonsson Comprehensive Cancer Center
        • Contatto:
          • Gottfried Konecny, MD
    • Colorado
      • Denver, Colorado, Stati Uniti, 80218
        • Reclutamento
        • Rocky Mountain Cancer Center
        • Contatto:
          • Allen Cohn, MD
    • Connecticut
      • New Haven, Connecticut, Stati Uniti, 06519
        • Reclutamento
        • Yale Cancer Center
        • Contatto:
          • Patricia LoRusso, MD
    • Delaware
      • Newark, Delaware, Stati Uniti, 19713
        • Reclutamento
        • Medical Oncology Hematology Consultants
        • Contatto:
          • Jamal Misleh, MD
    • Florida
      • Miami, Florida, Stati Uniti, 33136
        • Reclutamento
        • University of Miami - Sylvester Comprehensive Cancer Center
        • Contatto:
          • Gilberto de Lima Lopes Jr., MD
      • Orlando, Florida, Stati Uniti, 32803
        • Reclutamento
        • Advent Health
        • Contatto:
          • Robert Holloway, MD
      • Port Charlotte, Florida, Stati Uniti, 33980
        • Reclutamento
        • Florida Cancer Specialists South
        • Contatto:
          • Ivor Percent, MD
    • Massachusetts
      • Boston, Massachusetts, Stati Uniti, 02114
        • Reclutamento
        • Massachusetts General Hospital
        • Contatto:
          • Aparna Parikh, MD
      • Boston, Massachusetts, Stati Uniti, 02215
        • Reclutamento
        • Dana Farber Cancer Institute
        • Contatto:
          • Geoffrey Shapiro, MD, PhD
    • Michigan
      • Detroit, Michigan, Stati Uniti, 48201
        • Completato
        • Karmanos Cancer Institute
    • New York
      • New York, New York, Stati Uniti, 10065
        • Reclutamento
        • Memorial Sloan Kettering
        • Contatto:
          • Alison Schram, MD
      • New York, New York, Stati Uniti, 10032
        • Non ancora reclutamento
        • Columbia University Medical Center
        • Contatto:
          • June Hou, MD
    • North Carolina
      • Durham, North Carolina, Stati Uniti, 27705
        • Reclutamento
        • Duke University
        • Contatto:
          • Niharika Mettu, MD, PhD
    • Ohio
      • Cleveland, Ohio, Stati Uniti, 44195
        • Reclutamento
        • The Cleveland Clinic Taussig Cancer Center
        • Contatto:
          • Dale Shepard, MD
    • Oklahoma
      • Oklahoma City, Oklahoma, Stati Uniti, 73104
        • Reclutamento
        • University of Oklahoma
        • Contatto:
          • Debra Richardson, MD
    • Oregon
      • Portland, Oregon, Stati Uniti, 97210
        • Reclutamento
        • Oregon Health & Science University (OHSU)
        • Contatto:
          • Shivaani Kummar, MD
    • Pennsylvania
      • Philadelphia, Pennsylvania, Stati Uniti, 19104
        • Reclutamento
        • Abramson Cancer Center of the University of Pennsylvania
        • Contatto:
          • Lainie Martin, MD
      • Pittsburgh, Pennsylvania, Stati Uniti, 15213
        • Reclutamento
        • University of Pittsburgh Medical Center
        • Contatto:
          • Sarah Taylor, MD, PhD
      • York, Pennsylvania, Stati Uniti, 17403
        • Reclutamento
        • WellSpan York Cancer Center
        • Contatto:
          • Ikechukwu Akunyili, MD
    • South Carolina
      • Charleston, South Carolina, Stati Uniti, 29425
        • Terminato
        • Medical University of South Carolina
    • Tennessee
      • Nashville, Tennessee, Stati Uniti, 37203
        • Reclutamento
        • Sarah Cannon Research Institute
        • Contatto:
          • Melissa Johnson, MD
    • Texas
      • Austin, Texas, Stati Uniti, 78705
        • Reclutamento
        • New Experimental Therapeutics - NEXT Oncology
        • Contatto:
          • David Sommerhalder, MD
      • Bedford, Texas, Stati Uniti, 76022
        • Reclutamento
        • Texas Oncology
        • Contatto:
          • Terrence Wong, MD
      • Dallas, Texas, Stati Uniti, 75390
        • Reclutamento
        • UT Southwest Simmons Cancer Center
        • Contatto:
          • David Miller, MD
      • Houston, Texas, Stati Uniti, 77030
        • Reclutamento
        • The University of Texas MD Anderson Cancer Center
        • Contatto:
          • Ecaterina Dumbrava, MD
      • San Antonio, Texas, Stati Uniti, 78229
        • Reclutamento
        • New Experimental Therapeutics of San Antonio - NEXT Oncology
        • Contatto:
          • David Sommerhalder, MD
    • Virginia
      • Fairfax, Virginia, Stati Uniti, 22031
        • Reclutamento
        • Virginia Cancer Specialists
        • Contatto:
          • Alexander Spira, MD
    • Washington
      • Seattle, Washington, Stati Uniti, 98109
        • Reclutamento
        • University of Washington, Fred Hutchinson Cancer Center
        • Contatto:
          • Andrew Coveler, MD
    • Wisconsin
      • Madison, Wisconsin, Stati Uniti, 53705
        • Reclutamento
        • University of Wisconsin Carbone Cancer Center
        • Contatto:
          • Nataliya Uboha, MD, PhD

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

12 anni e precedenti (Bambino, Adulto, Adulto più anziano)

Accetta volontari sani

No

Sessi ammissibili allo studio

Tutto

Descrizione

Inclusion Criteria:

  • At least 18 years of age or 12 to 17 years of age after Safety Review Committee approval.
  • Locally advanced or metastatic solid malignancy with a TP53 Y220C mutation
  • Eastern Cooperative Oncology Group (ECOG) status of 0 or 1
  • Previously treated with one or more lines of anticancer therapy and progressive disease
  • Adequate organ function
  • Measurable disease per RECIST v1.1 (Phase 2)

Additional Criteria for Inclusion in Phase 1b (rezatapopt) + pembrolizumab combination)

  • Anti-PD-1/PD-L1 naive or must have progressed on treatment
  • Measurable disease

Exclusion Criteria:

  • Anti-cancer therapy within 21 days (or 5 half-lives) of receiving the study drug
  • Radiotherapy within 14 days of receiving the study drug
  • Primary CNS tumor
  • History of leptomeningeal disease or spinal cord compression
  • Brain metastases, unless neurologically stable and do not require steroids to treat associated neurological symptoms
  • Stroke or transient ischemic attack within 6 months prior to screening
  • Heart conditions such as unstable angina within 6 months prior to screening, uncontrolled hypertension, a heart attack within 6 months prior to screening, congestive heart failure, prolongation of QT interval, or other rhythm abnormalities
  • Strong CYP3A4 inducers and strong CYP2C9 inhibitors/inducers within 14 days of first dose of rezatapopt
  • History of gastrointestinal (GI) disease that may interfere with absorption of study drug or patients unable to take oral medication
  • History of prior organ transplant
  • Known, active malignancy, except for treated cervical intraepithelial neoplasia, or non-melanoma skin cancer
  • Known, active uncontrolled Hepatitis B, Hepatitis C, or human immunodeficiency virus infection

Additional Criteria for Exclusion from Phase 2 (rezatapopt monotherapy)

  • Known KRAS mutation, defined as a single nucleotide variant (SNV) (Phase 2). Exception: Ovarian cancer patients with a known KRAS SNV are permitted.

Additional Criteria for Exclusion from Phase 1b (rezatapopt) + pembrolizumab combination)

  • Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor and discontinued from that treatment due to a Grade 3 or higher immune-related AE (irAE)
  • Received a live or live-attenuated vaccine within 30 days prior to the first dose of study intervention
  • Diagnosis of immunodeficiency or receiving chronic systemic steroid therapy within 7 days prior to the first dose of study drug
  • Hypersensitivity (≥ Grade 3) to pembrolizumab and/or any of its excipients
  • Active autoimmune disease that has required systemic treatment in past 2 years
  • History of radiation pneumonitis
  • History of (non-infectious) or active pneumonitis / interstitial lung disease that required steroids
  • Active infection requiring systemic therapy
  • Known history of HIV infection
  • Has previously received rezatapopt

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: Non randomizzato
  • Modello interventistico: Assegnazione parallela
  • Mascheramento: Nessuno (etichetta aperta)

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: Phase 1 Monotherapy Dose Escalation

Multiple dose levels of daily oral rezatapopt will be evaluated in an escalating manner, to determine the maximum tolerated dose and to ensure sufficient safety experience, pharmacokinetic information, and early evidence of clinical activity of rezatapopt to recommend a Phase 2 dose (RP2D).
Droga: rezatapopt

First-in-class, oral, small molecule p53 reactivator selective for the TP53 Y220C mutation.

Altri nomi:
  • PC14586
Sperimentale: Phase 1b Combination Therapy Dose Escalation, Part 1

Multiple dose levels of daily oral rezatapopt in combination with a stable dose of pembrolizumab (200 mg IV q3 weeks) will be evaluated in an escalating manner, to determine the maximum tolerated dose and to ensure sufficient safety experience, pharmacokinetic information, and early evidence of clinical activity of PC14586 to recommend a Phase 2 dose (RP2D) of rezatapopt when administered in combination with pembrolizumab.
Droga: rezatapopt

First-in-class, oral, small molecule p53 reactivator selective for the TP53 Y220C mutation.

Altri nomi:
  • PC14586
Droga: pembrolizumab

Participants receive pembrolizumab 200 mg by intravenous (IV) infusion over 30 minutes.

Altri nomi:
  • MK-3475
  • KEYTRUDA®
  • NOTA CHIAVE-D79
  • MK-3475-D79
Sperimentale: Phase 1b Combination Therapy Dose Expansion, PD(L)-1 naive patients

Additional (expansion of) participants will enroll at the RP2D of daily oral PC14586 (INN: rezatapopt) when administered in combination with pembrolizumab (200 mg IV q3 weeks) for continued evaluation. Participants will have advanced solid tumors harboring a p53 Y220C mutation and are PD(L)-1 naive patients.
Droga: rezatapopt

First-in-class, oral, small molecule p53 reactivator selective for the TP53 Y220C mutation.

Altri nomi:
  • PC14586
Droga: pembrolizumab

Participants receive pembrolizumab 200 mg by intravenous (IV) infusion over 30 minutes.

Altri nomi:
  • MK-3475
  • KEYTRUDA®
  • NOTA CHIAVE-D79
  • MK-3475-D79
Sperimentale: Phase 1b Combination Therapy Dose Expansion, PD(L)-1 relapsed/refractory patients

Additional (expansion of) participants will enroll at the RP2D of daily oral rezatapopt when administered in combination with pembrolizumab (200 mg IV q3 weeks) for continued evaluation. Participants will have advanced solid tumors harboring a p53 Y220C mutation and are PD(L)-1 relapsed/refractory patients.
Droga: rezatapopt

First-in-class, oral, small molecule p53 reactivator selective for the TP53 Y220C mutation.

Altri nomi:
  • PC14586
Droga: pembrolizumab

Participants receive pembrolizumab 200 mg by intravenous (IV) infusion over 30 minutes.

Altri nomi:
  • MK-3475
  • KEYTRUDA®
  • NOTA CHIAVE-D79
  • MK-3475-D79
Sperimentale: Phase 2 Monotherapy Dose Expansion, Ovarian Cancer Cohort

Additional (expansion of) participants will dose with 2000 mg daily oral PC14586 (INN: rezatapopt) with food for continued evaluation. Ovarian Cancer Cohort participants will have locally advanced or metastatic ovarian cancer harboring a TP53 Y220C mutation who meet all eligibility criteria and have measurable disease per RECIST 1.1.
Droga: rezatapopt

First-in-class, oral, small molecule p53 reactivator selective for the TP53 Y220C mutation.

Altri nomi:
  • PC14586
Sperimentale: Phase 2 Monotherapy Dose Expansion, Lung Cancer Cohort

Additional (expansion of) participants will dose with 2000 mg daily oral PC14586 (INN: rezatapopt) with food for continued evaluation. Lung Cancer Cohort participants will have locally advanced or metastatic lung cancer harboring a TP53 Y220C mutation who meet all eligibility criteria and have measurable disease per RECIST 1.1.
Droga: rezatapopt

First-in-class, oral, small molecule p53 reactivator selective for the TP53 Y220C mutation.

Altri nomi:
  • PC14586
Sperimentale: Phase 2 Monotherapy Dose Expansion, Breast Cancer Cohort

Additional (expansion of) participants will dose with 2000 mg daily oral PC14586 (INN: rezatapopt) with food for continued evaluation. Breast Cancer Cohort participants will have locally advanced or metastatic breast cancer harboring a TP53 Y220C mutation who meet all eligibility criteria and have measurable disease per RECIST 1.1.
Droga: rezatapopt

First-in-class, oral, small molecule p53 reactivator selective for the TP53 Y220C mutation.

Altri nomi:
  • PC14586
Sperimentale: Phase 2 Monotherapy Dose Expansion, Endometrial Cancer Cohort

Additional (expansion of) participants will dose with 2000 mg daily oral PC14586 (INN: rezatapopt) with food for continued evaluation. Endometrial Cancer Cohort participants will have locally advanced or metastatic endometrial cancer harboring a TP53 Y220C mutation who meet all eligibility criteria and have measurable disease per RECIST 1.1.
Droga: rezatapopt

First-in-class, oral, small molecule p53 reactivator selective for the TP53 Y220C mutation.

Altri nomi:
  • PC14586
Sperimentale: Phase 2 Monotherapy Dose Expansion, Other Solid Tumors Cohort

Additional (expansion of) participants will dose with 2000 mg daily oral PC14586 (INN: rezatapopt) with food for continued evaluation. Other Solid Tumors Cohort participants will have locally advanced or metastatic solid tumors harboring a TP53 Y220C mutation who meet all eligibility criteria and have measurable disease per RECIST 1.1.
Droga: rezatapopt

First-in-class, oral, small molecule p53 reactivator selective for the TP53 Y220C mutation.

Altri nomi:
  • PC14586

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Phase 1 Monotherapy (Dose Escalation): Determine the number and type of adverse events to characterize the safety of rezatapopt
Lasso di tempo: 40 months

Number of participants with treatment related adverse events
40 months
Phase 1 Monotherapy (Dose Escalation): Establish the Recommended Phase 2 Dose (RP2D)
Lasso di tempo: 30 months

RP2D will be determined using available safety and pharmacokinetics and pharmacodynamics data
30 months
Phase 1 Monotherapy (Dose Escalation): Establish the maximum tolerated dose (MTD) (Phase 1)
Lasso di tempo: The first 28 days of treatment (Cycle 1) per patient

Incidence of dose limiting toxicities (DLTs) during the first 28 days of treatment with rezatapopt
The first 28 days of treatment (Cycle 1) per patient
Phase 1b Combination Therapy (Part 1: Dose Escalation): Determine the number and type of adverse events to characterize the safety of rezatapopt when administered in combination with pembrolizumab
Lasso di tempo: 18 months for treatment arm

Number of participants with treatment related adverse events
18 months for treatment arm
Phase 1b Combination Therapy (Part 1: Dose Escalation): Establish the maximum tolerated dose (MTD) of rezatapopt when administered in combination with pembrolizumab
Lasso di tempo: The first 28 days of combination treatment arm (starting on Day -7) per patient

Incidence of dose limiting toxicities (DLTs) during the first 28 days of treatment with rezatapopt
The first 28 days of combination treatment arm (starting on Day -7) per patient
Phase 1b Combination Therapy (Part 1: Dose Escalation): Establish the Recommended Phase 2 Dose (RP2D) of rezatapopt when administered in combination with pembrolizumab
Lasso di tempo: 18 months

RP2D will be determined using available safety and pharmacokinetics and pharmacodynamics data
18 months
Phase 1b Combination Therapy (Part 2: Dose Expansion): Determine the number and type of adverse events to characterize the safety of rezatapopt when administered in combination with pembrolizumab
Lasso di tempo: 12 months for treatment arm

Number of participants with treatment related adverse events
12 months for treatment arm
Phase 2 Monotherapy (Dose Expansion): Response rate assessment to evaluate the clinical activity / efficacy of rezatapopt
Lasso di tempo: 34 months

Overall response rate in accordance with Response Evaluation Criteria (RECIST) v.1.1 as assessed by independent review across all cohorts
34 months
Phase 2 Monotherapy (Dose Expansion): Response rate assessment to evaluate the clinical activity / efficacy of rezatapopt in ovarian cancer patients
Lasso di tempo: 34 months

Overall response rate in accordance with Response Evaluation Criteria (RECIST) v.1.1 as assessed by independent review in the ovarian cancer cohort
34 months

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Phase 1 Monotherapy: PK profile of rezatapopt - Peak concentration (Cmax)
Lasso di tempo: Approximately 12 months per patient (75 months for Phase 1 and Phase 2)

Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of rezatapopt
Approximately 12 months per patient (75 months for Phase 1 and Phase 2)
Phase 1 Monotherapy: PK profile of rezatapopt - Time of peak concentration (Tmax)
Lasso di tempo: Approximately 12 months per patient (75 months for Phase 1 and Phase 2)

Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of rezatapopt
Approximately 12 months per patient (75 months for Phase 1 and Phase 2)
Phase 1 Monotherapy: PK profile of rezatapopt - Area under the plasma concentration-time curve from time zero to time of last sampling timepoint (AUC0-t)
Lasso di tempo: Approximately 12 months per patient (75 months for Phase 1 and Phase 2)

Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of rezatapopt
Approximately 12 months per patient (75 months for Phase 1 and Phase 2)
Phase 1 Monotherapy: PK profile of rezatapopt - Area under the plasma concentration-time curve in one dosing interval (AUCtau)
Lasso di tempo: Approximately 12 months per patient (75 months for Phase 1 and Phase 2)

Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of rezatapopt
Approximately 12 months per patient (75 months for Phase 1 and Phase 2)
Phase 1 Monotherapy: PK profile of rezatapopt - Trough observed concentrations (Ctrough/Ctau)
Lasso di tempo: Approximately 12 months per patient (75 months for Phase 1 and Phase 2)

Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of rezatapopt
Approximately 12 months per patient (75 months for Phase 1 and Phase 2)
Phase 1 Monotherapy: Blood plasma assessment to describe the concentration of PC14586 and metabolites when rezatapopt is administered orally.
Lasso di tempo: Approximately 12 months per patient (75 months for Phase 1 and Phase 2)

Blood plasma concentration
Approximately 12 months per patient (75 months for Phase 1 and Phase 2)
Phase 1 Monotherapy (Dose Escalation): Overall Response Rate per RECIST v1.1 or PCWG3 modified RECIST v1.1
Lasso di tempo: 41 months for study (end of Phase 1)

Evaluation of preliminary anti-tumor activity of rezatapopt as a single agent
41 months for study (end of Phase 1)
Phase 1 Monotherapy (Dose Escalation): Time to Response per RECIST v1.1 or PCWG3 modified RECIST v1.1
Lasso di tempo: 41 months for study (end of Phase 1)

Evaluation of preliminary anti-tumor activity of rezatapopt as a single agent
41 months for study (end of Phase 1)
Phase 1 Monotherapy (Dose Escalation): Duration of Response per RECIST v1.1 or PCWG3 modified RECIST v1.1
Lasso di tempo: 41 months for study (end of Phase 1)

Evaluation of preliminary anti-tumor activity of rezatapopt as a single agent
41 months for study (end of Phase 1)
Phase 1 Monotherapy (Dose Escalation): Disease Control Rate per RECIST v1.1 or PCWG3 modified RECIST v1.1
Lasso di tempo: 41 months for study (end of Phase 1)

Evaluation of preliminary anti-tumor activity of rezatapopt as a single agent
41 months for study (end of Phase 1)
Phase 1 Monotherapy (Dose Escalation): Progression Free Survival per RECIST v1.1 or PCWG3 modified RECIST v1.1
Lasso di tempo: 41 months for study (end of Phase 1)

Evaluation of preliminary anti-tumor activity of rezatapopt as a single agent
41 months for study (end of Phase 1)
Phase 1 Monotherapy (Dose Escalation): Overall Survival
Lasso di tempo: 41 months for study (end of Phase 1)

Evaluation of preliminary anti-tumor activity of rezatapopt as a single agent
41 months for study (end of Phase 1)
Phase 1b Combination Therapy: PK profile of rezatapopt in combination with pembrolizumab - Peak concentration (Cmax)
Lasso di tempo: Approximately 12 months per patient (30 months for treatment arm)

Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of rezatapopt
Approximately 12 months per patient (30 months for treatment arm)
Phase 1b Combination Therapy: PK profile of rezatapopt in combination with pembrolizumab - Time of peak concentration (Tmax)
Lasso di tempo: Approximately 12 months per patient (30 months for treatment arm)

Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of rezatapopt
Approximately 12 months per patient (30 months for treatment arm)
Phase 1b Combination Therapy: PK profile of rezatapopt in combination with pembrolizumab - Area under the plasma concentration-time curve from time zero to time of last sampling timepoint (AUC0-t)
Lasso di tempo: Approximately 12 months per patient (30 months for treatment arm)

Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of rezatapopt
Approximately 12 months per patient (30 months for treatment arm)
Phase 1b Combination Therapy: PK profile of rezatapopt in combination with pembrolizumab - Area under the plasma concentration-time curve in one dosing interval (AUCtau)
Lasso di tempo: Approximately 12 months per patient (30 months for treatment arm)

Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of rezatapopt
Approximately 12 months per patient (30 months for treatment arm)
Phase 1b Combination Therapy: PK profile of rezatapopt in combination with pembrolizumab - Trough observed concentrations (Ctrough/Ctau)
Lasso di tempo: Approximately 12 months per patient (30 months for treatment arm)

Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of rezatapopt
Approximately 12 months per patient (30 months for treatment arm)
Phase 1b Combination Therapy: Blood plasma assessment to describe the concentration of rezatapopt and metabolites when rezatapopt is administered orally in combination with pembrolizumab.
Lasso di tempo: Approximately 12 months per patient (30 months for treatment arm)

Blood plasma concentration
Approximately 12 months per patient (30 months for treatment arm)
Phase 1b Combination Therapy: Overall Response Rate per RECIST v1.1, iRECIST, or PCWG3 as assessed by Investigator and as assessed by independent review
Lasso di tempo: 30 months for study (end of Phase 1b)

Evaluation of anti-tumor activity of rezatapopt in combination with pembrolizumab
30 months for study (end of Phase 1b)
Phase 1b Combination Therapy: Time to Response per RECIST v1.1, iRECIST, or PCWG3 as assessed by Investigator and as assessed by independent review
Lasso di tempo: 30 months for study (end of Phase 1b)

Evaluation of anti-tumor activity of rezatapopt in combination with pembrolizumab
30 months for study (end of Phase 1b)
Phase 1b Combination Therapy: Duration of Response per RECIST v1.1, iRECIST, or PCWG3 as assessed by Investigator and as assessed by independent review
Lasso di tempo: 30 months for study (end of Phase 1b)

Evaluation of anti-tumor activity of rezatapopt in combination with pembrolizumab
30 months for study (end of Phase 1b)
Phase 1b Combination Therapy: Disease Control Rate per RECIST v1.1, iRECIST, or PCWG3 as assessed by Investigator and as assessed by independent review
Lasso di tempo: 30 months for study (end of Phase 1b)

Evaluation of anti-tumor activity of rezatapopt in combination with pembrolizumab
30 months for study (end of Phase 1b)
Phase 1b Combination Therapy: Overall Survival
Lasso di tempo: 30 months for study (end of Phase 1b)

Evaluation of anti-tumor activity of rezatapopt in combination with pembrolizumab
30 months for study (end of Phase 1b)
Phase 1b Combination Therapy: Determine the number and type of adverse events to characterize the safety of rezatapopt
Lasso di tempo: 30 months for study (end of Phase 1b)

Number of participants with treatment related adverse events
30 months for study (end of Phase 1b)
Phase 1b Combination Therapy: Progression Free Survival per RECIST v1.1, iRECIST, or PCWG3 as assessed by Investigator and as assessed by independent review
Lasso di tempo: 30 months for study (end of Phase 1b)

Evaluation of anti-tumor activity of rezatapopt in combination with pembrolizumab
30 months for study (end of Phase 1b)
Phase 2 Monotherapy: PK profile of rezatapopt - Time of peak concentration (Tmax)
Lasso di tempo: Approximately 12 months per patient (75 months for Phase 1 and Phase 2)

Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of rezatapopt
Approximately 12 months per patient (75 months for Phase 1 and Phase 2)
Phase 2 Monotherapy: PK profile of rezatapopt - Peak concentration (Cmax)
Lasso di tempo: Approximately 12 months per patient (75 months for Phase 1 and Phase 2)

Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of rezatapopt
Approximately 12 months per patient (75 months for Phase 1 and Phase 2)
Phase 2 Monotherapy: PK profile of rezatapopt - Area under the plasma concentration-time curve from time zero to time of last sampling timepoint (AUC0-t)
Lasso di tempo: Approximately 12 months per patient (75 months for Phase 1 and Phase 2)

Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of rezatapopt
Approximately 12 months per patient (75 months for Phase 1 and Phase 2)
Phase 2 Monotherapy: PK profile of rezatapopt - Area under the plasma concentration-time curve in one dosing interval (AUCtau)
Lasso di tempo: Approximately 12 months per patient (75 months for Phase 1 and Phase 2)

Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of rezatapopt
Approximately 12 months per patient (75 months for Phase 1 and Phase 2)
Phase 2 Monotherapy: PK profile of rezatapopt - Trough observed concentrations (Ctrough/Ctau)
Lasso di tempo: Approximately 12 months per patient (75 months for Phase 1 and Phase 2)

Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of rezatapopt
Approximately 12 months per patient (75 months for Phase 1 and Phase 2)
Phase 2 Monotherapy: Blood plasma assessment to describe the concentration of rezatapopt and metabolites when rezatapopt is administered orally.
Lasso di tempo: Approximately 12 months per patient (75 months for Phase 1 and Phase 2)

Blood plasma concentration
Approximately 12 months per patient (75 months for Phase 1 and Phase 2)
Phase 2 Monotherapy (Dose Expansion): Determine the number and type of adverse events to characterize the safety of rezatapopt
Lasso di tempo: 34 months for study (end of Phase 2)

Number of participants with treatment related adverse events
34 months for study (end of Phase 2)
Phase 2 Monotherapy (Dose Expansion): Overall Response Rate across all cohorts per RECIST v1.1 as assessed by Investigator
Lasso di tempo: 34 months for study (end of Phase 2)

Evaluation of anti-tumor activity of rezatapopt as a single agent
34 months for study (end of Phase 2)
Phase 2 Monotherapy (Dose Expansion): Overall Response Rate in ovarian cancer cohort per RECIST v1.1 as assessed by Investigator
Lasso di tempo: 34 months for study (end of Phase 2)

Evaluation of anti-tumor activity of rezatapopt as a single agent
34 months for study (end of Phase 2)
Phase 2 Monotherapy (Dose Expansion): Time to Response in ovarian cancer cohort per RECIST v1.1 as assessed by Investigator and as assessed by independent review
Lasso di tempo: 34 months for study (end of Phase 2)

Evaluation of anti-tumor activity of rezatapopt as a single agent
34 months for study (end of Phase 2)
Phase 2 Monotherapy (Dose Expansion): Time to Response across all cohorts per RECIST v1.1 as assessed by Investigator and as assessed by independent review
Lasso di tempo: 34 months for study (end of Phase 2)

Evaluation of anti-tumor activity of rezatapopt as a single agent
34 months for study (end of Phase 2)
Phase 2 Monotherapy (Dose Expansion): Duration of Response in ovarian cancer cohort per RECIST v1.1 as assessed by Investigator and as assessed by independent review
Lasso di tempo: 34 months for study (end of Phase 2)

Evaluation of anti-tumor activity of rezatapopt as a single agent
34 months for study (end of Phase 2)
Phase 2 Monotherapy (Dose Expansion): Duration of Response across all cohorts per RECIST v1.1 as assessed by Investigator and as assessed by independent review
Lasso di tempo: 34 months for study (end of Phase 2)

Evaluation of anti-tumor activity of rezatapopt as a single agent
34 months for study (end of Phase 2)
Phase 2 Monotherapy (Dose Expansion): Disease Control Rate in ovarian cancer cohort per RECIST v1.1 as assessed by Investigator and as assessed by independent review
Lasso di tempo: 34 months for study (end of Phase 2)

Evaluation of anti-tumor activity of rezatapopt as a single agent
34 months for study (end of Phase 2)
Phase 2 Monotherapy (Dose Expansion): Disease Control Rate across all cohorts per RECIST v1.1 as assessed by Investigator and as assessed by independent review
Lasso di tempo: 34 months for study (end of Phase 2)

Evaluation of anti-tumor activity of rezatapopt as a single agent
34 months for study (end of Phase 2)
Phase 2 Monotherapy (Dose Expansion): Progression Free Survival in ovarian cancer cohort per RECIST v1.1 as assessed by Investigator and as assessed by independent review
Lasso di tempo: 34 months for study (end of Phase 2)

Evaluation of anti-tumor activity of rezatapopt as a single agent
34 months for study (end of Phase 2)
Phase 2 Monotherapy (Dose Expansion): Progression Free Survival across all cohorts per RECIST v1.1 as assessed by Investigator and as assessed by independent review
Lasso di tempo: 34 months for study (end of Phase 2)

Evaluation of anti-tumor activity of rezatapopt as a single agent
34 months for study (end of Phase 2)
Phase 2 Monotherapy (Dose Expansion): Overall Survival in ovarian cancer cohort
Lasso di tempo: 34 months for study (end of Phase 2)

Evaluation of anti-tumor activity of rezatapopt as a single agent
34 months for study (end of Phase 2)
Phase 2 Monotherapy (Dose Expansion): Overall Survival across all cohorts
Lasso di tempo: 34 months for study (end of Phase 2)

Evaluation of anti-tumor activity of rezatapopt as a single agent
34 months for study (end of Phase 2)
Phase 2 Monotherapy (Dose Expansion): Quality of life assessment
Lasso di tempo: Evaluated at every visit. 34 months for treatment arm (end of Phase 2)

Changes from baseline in quality of life as measured by a validated instrument, for participants 18 and older
Evaluated at every visit. 34 months for treatment arm (end of Phase 2)

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

PMV Pharmaceuticals, Inc

Collaboratori

Merck Sharp & Dohme LLC

Investigatori

  • Direttore dello studio: Marc Fellous, MD, Sr. Vice President, Clinical Development and Medical Affairs

Pubblicazioni e link utili

La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.

Pubblicazioni generali

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio (Effettivo)

29 ottobre 2020

Completamento primario (Stimato)

15 dicembre 2026

Completamento dello studio (Stimato)

31 dicembre 2027

Date di iscrizione allo studio

Primo inviato

1 ottobre 2020

Primo inviato che soddisfa i criteri di controllo qualità

7 ottobre 2020

Primo Inserito (Effettivo)

14 ottobre 2020

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

2 ottobre 2026

Ultimo aggiornamento inviato che soddisfa i criteri QC

1 ottobre 2026

Ultimo verificato

1 ottobre 2026

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • PMV-586-101
  • KEYNOTE-D79 (Identificatore di registro: Merck, Sharp & Dohme, LLC)
  • MK-3475-D79 (Identificatore di registro: Merck, Sharp & Dohme, LLC)

Piano per i dati dei singoli partecipanti (IPD)

Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?

NO

Informazioni su farmaci e dispositivi, documenti di studio

Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti

Sì

Studia un dispositivo regolamentato dalla FDA degli Stati Uniti

No

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

Sottoscrivi